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Issue 1, 2013
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Localization of copper and copper transporters in the human brain

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Abstract

Disturbances in brain copper result in rare and severe neurological disorders and may play a role in the pathogenesis and progression of multiple neurodegenerative diseases. Our current understanding of mammalian brain copper transport is based on model systems outside the central nervous system and no data are available regarding copper transport systems in the human brain. To address this deficit, we quantified regional copper concentrations and examined the distribution and cellular localization of the copper transport proteins Copper transporter 1, Atox1, ATP7A, and ATP7B in multiple regions of the human brain using inductively coupled plasma-mass spectrometry, Western blot and immunohistochemistry. We identified significant relationships between copper transporter levels and brain copper concentrations, supporting a role for these proteins in copper transport in the human brain. Interestingly, the substantia nigra contained twice as much copper than that in other brain regions, suggesting an important role for copper in this brain region. Furthermore, ATP7A levels were significantly greater in the cerebellum, compared with other brain regions, supporting an important role for ATP7A in cerebellar neuronal health. This study provides novel data regarding copper regulation in the human brain, critical to understand the mechanisms by which brain copper levels can be altered, leading to neurological disease.

Graphical abstract: Localization of copper and copper transporters in the human brain

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Publication details

The article was received on 26 Jul 2012, accepted on 03 Oct 2012 and first published on 03 Oct 2012


Article type: Paper
DOI: 10.1039/C2MT20151H
Citation: Metallomics, 2013,5, 43-51

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    Localization of copper and copper transporters in the human brain

    K. M. Davies, D. J. Hare, V. Cottam, N. Chen, L. Hilgers, G. Halliday, J. F. B. Mercer and K. L. Double, Metallomics, 2013, 5, 43
    DOI: 10.1039/C2MT20151H

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